Papovaviruses are virtually universal, usually benign agents in human populations. In immunologically impaired patients, however, this group of viruses is capable of causing a rare, fatal, central nervous system infection, progressive multifocal leukoencephalopathy (PML) and has been associated by some investigators with neoplastic disease. Little is known however, about the pathogenesis of papovavirus infection in man or about the conditions under which members of this usually benign group of viruses may cause clinical significant human disease. The study currently in progress involves the investigation of an analogous papovavirus, K virus of mice, in its natural host as a possible model for human infection. The study has defined the probable natural route of transmission for the virus as well as the pathogenesis of acute K virus infection of suckling, weanling, and adult mice. It has been shown that K virus causes a persistent infection which can be reactivated by immunosuppression. During the remaining year further experiments will be carried out concerning K virus infection in immunosuppressed animals, the ability of the virus to cause transplacental infection, and the oncogenic properties of the virus in vivo and in vitro. The experience will be carried out using histologic techniques and fluorescent antibody studies of infected tissues. Viral concentrations in individual infected organs will be determined by a fluorescent antibody assay developed by the principal investigator, employing primary cultures of mouse embryo cells.